Cited by 344Diabetes, Cardiovascular Risks, and LipoproteinsMetabolism, Diabetes, and CancerPancreatic function and diabetes

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Effects of fat on glucose uptake and utilization in patients with non-insulin-dependent diabetes.

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Boden, G, Chen, X·1995·Journal of Clinical Investigation

DOI 10.1172/jci118160PMC PMC185747

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Abstract

It was the aim of this study to determine whether FFA inhibit insulin-stimulated whole body glucose uptake and utilization in patients with non-insulin-dependent diabetes. We performed five types of isoglycemic (approximately 11mM) clamps: (a) with insulin; (b) with insulin plus fat/heparin; (c) with insulin plus glycerol; (d) with saline; (e) with saline plus fat/heparin and two types of euglycemic (approximately 5mM) clamps: (a) with insulin; (b) with insulin plus fat/heparin. During these studies, we determined rates of glucose uptake, glycolysis (both with 3[3H] glucose), glycogen synthesis (determined as glucose uptake minus glycolysis), carbohydrate oxidation (by indirect calorimetry) and nonoxidative glycolysis (determined as glycolysis minus carbohydrate oxidation). Fat/heparin infusion did not affect basal glucose uptake, but inhibited total stimulated (insulin stimulated plus basal) glucose uptake by 40-50% in isoglycemic and in euglycemic patients at plasma FFA concentration of approximately 950 and approximately 550 microM, respectively. In isoglycemic patients, the 40-50% inhibition of total stimulated glucose uptake was due to near complete inhibition of the insulin-stimulated part of glucose uptake. Proportional inhibition of glucose uptake, glycogen synthesis, and glycolysis suggested a major FFA-mediated defect involving glucose transport and/or phosphorylation. In summary, fat produced proportional inhibitions of insulin-stimulated glucose uptake and of intracellular glucose utilization. We conclude, that physiologically elevated levels of FFa could potentially be responsible for a large part of the peripheral insulin resistance in patients with non-insulin-dependent diabetes mellitus.

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Authors: Boden, G., & Chen, X.
Affiliations: Temple University (US)
ORCID: Chen, X
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1995-09-01
Volume: 96
Issue: 3
Pages: 1261-1268
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci118160
PMC: PMC185747
OpenAlex: W2115830695
Cited by: 344
References: 39
Citations by year: 2026: 1 · 2025: 4 · 2024: 6 · 2023: 9 · 2022: 5 · 2021: 4 · 2020: 7 · 2019: 6 · 2018: 8 · 2017: 13 · 2016: 6 · 2015: 13 · 2014: 8 · 2013: 9 · 2012: 14
FWCI: 5.28
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: American Diabetes Association
National Institutes of Health (5r01ag007988-10)
National Institute on Aging (R01-AG07988)
National Center for Research Resources (M01RR000349, RR-00349)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Keywords: free fatty acids, insulin resistance, type 2 diabetes, insulin-stimulated glucose uptake, glucose utilization, glucose transport, glycogen synthesis, glycolysis, carbohydrate oxidation, heparin, fat infusion
MeSH terms: Aged, Analysis of Variance, Blood Glucose, Diabetes Mellitus, Type 2, Emulsions, Fat Emulsions, Intravenous, Fatty Acids, Nonesterified, Female, Glucagon, Glucose, Heparin, Humans, Infusions, Intravenous, Insulin, Isophane, Male, Middle Aged, Phospholipids, Recombinant Proteins, Safflower Oil, Soybean Oil, Glucose Clamp Technique

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Effects of fat on glucose uptake and utilization in patients with non-insulin-dependent diabetes.

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